CN116472016A

CN116472016A - Compression device

Info

Publication number: CN116472016A
Application number: CN202180078784.8A
Authority: CN
Inventors: A·汉农; B·奥利维拉; M·奥哈洛伦
Original assignee: National University of Ireland Galway NUI
Current assignee: National University of Ireland Galway NUI
Priority date: 2020-10-27
Filing date: 2021-10-27
Publication date: 2023-07-21
Also published as: JP2023547190A; CA3196004A1; KR20230098248A; AU2021370372A1; MX2023004746A; US20230390145A1; EP4236884A2; WO2022090346A3; WO2022090346A2

Abstract

A medical device comprising a balloon (or balloons), an attachment mechanism, a fluid inlet, a fluid outlet, a compressor, a pressure regulator system, and an infusion sensor, is compressed against intact tissue (unbroken skin or surface tissue in a cavity) in order to minimize blood infusion to prevent delivery of drugs to non-target sites.

Description

Compression device

Technical Field

The present invention relates to a pneumatic pressure device configured to reduce the likelihood of chemotherapy-induced side effects in a subject, including, but not limited to, chemotherapy-induced alopecia (CIA), infertility, and peripheral neuropathy.

Background

Chemotherapy is one of the most widely used therapies for cancer, and 980 world-wide patients were estimated to be treated with a chemotherapy regimen in 2018. Chemotherapy works by targeting the known properties of rapidly growing, rapidly proliferating cells-cancer cells. This demonstrates the effectiveness of chemotherapy in cancer therapy and also demonstrates several side effects of chemotherapy treatment resulting from systemic delivery of chemotherapeutic agents.

Many non-cancerous cells that are normally present in the body have the property of dividing rapidly. This results in several recognized side effects of cancer treatment, such as chemotherapy-induced alopecia (CIA), chemotherapy-induced peripheral neuropathy (CIPN), and chemotherapy-induced infertility (CII), among others. In the expectation that the use of 2040 years of chemotherapy will increase by 53%, there is an urgent need to deal with the side effects of this cancer treatment core element.

Chemotherapy-induced alopecia (CIA) affects at least 450 tens of thousands of people per year and is considered by patients as the most invasive aspect in cancer treatment. CIA is a clear physical symptom of cancer treatment, and it is a continuous reminder for patients with disease, with negative psychological impact on the patient. For example, 47% of female breast cancer patients consider CIA as the most invasive aspect of chemotherapy.

250 tens of thousands of women experience each year may result in treatment of CIA, with more than 100 tens of thousands of people in this group experiencing breast cancer treatment, and another 120 tens of thousands experiencing solid tumor treatment. More and more patients and clinicians have recognized the need for CIA treatment, thereby raising increased attention to developing prophylactic solutions.

Methods for preventing CIA have been marketed for over 20 years in the form of "cold cap" therapies that use dry ice/gel and a head covering cap to induce contraction of scalp blood vessels, thereby preventing the destructive effects of chemotherapeutic agents on hair follicles. Over the past many years, the "scalp cooling" technique has been developed, which is a more modern, FDA-approved machine-based cooling therapy. Scalp cooling is becoming increasingly popular due to its reduced treatment time and relatively simple use compared to cold caps using the same principle of operation.

The cold cap and scalp cooling cap are typically head covering caps that are filled with dry ice in the case of manual caps or are connected to a circulating coolant system in the case of scalp coolers. The mechanism of action is expected to be that the reduced tissue temperature causes vasoconstriction in local blood vessels, thereby restricting blood flow to the hair follicle. In addition, the reduced temperature also causes a decrease in the metabolic rate of cells in the scalp region. This combined effect causes a reduced level of chemotherapy on the hair follicle and thus reduces hair loss. Examples of scalp cooling techniques can be found in published handbook WO 2019/222044 and U.S. patent No. 10,478,637B2.

US 7744640 describes a wound treatment device which is adapted to the shape of the scalp. The hollow conduit is configured to receive the pumped air or gaseous fluid as part of a thermal conditioning system. The tubing is arranged in a series of loops or similar configuration so that any type of fluid can be pumped through the system while providing a large contact area to the scalp for imparting a temperature change or maintaining a temperature on the scalp surface. GB 2417423 describes a cooling and pressure applying device to relieve migraine. The device consists of a tube wrapped around the scalp in a hemispherical shape. WO 03/047479 describes a cap for covering a scalp cooling device that can act as a mechanism for attaching the scalp cooling device to a wearer. US 21019/26223 describes therapeutic vibration devices that can use flexible balloons. In this case, the balloon is used to secure the device to the head of the user. There is always a vibrating element between the wearer and the balloon so that the balloon does not directly contact the therapeutic effect. Compression is not used here for any therapeutic effect, its function being merely to fix the device in place. WO 96/10983 describes a scalp blood irrigation device that uses pressure to increase blood flow to promote hair growth and combat androgenic alopecia, commonly known as pattern baldness.

There are several problems with current treatments. Scalp hypothermia techniques are extremely uncomfortable for the patient. Of the clinical data disclosed by manufacturers of commercially available scalp cooling systems, 42% complain of headache, and 74% report scalp pain induced by cooling. The desire for more tolerable treatments is a key driver of the destructive solution to this need for all relevant stakeholders. Treatment centers suffer from opportunity costs due to the length of additional treatment time required-the availability of time slots for scalp cooling treatment may be a limiting factor in the number of additional chemotherapeutic patients that can be treated in the clinic.

The tourniquet system modeled with a surgical tourniquet to pressurize the head Pi Shi was studied in 1970 s and 1980 s and then stopped due to obsolescence, adverse effects, and potential discomfort and risk to the patient, as the system applies a single point of pressure at extremely high levels.

Infection transfer also causes additional problems. The scalp cooling cap surrounds the chin area of the patient, meaning that body fluids left on the non-washable cap may lead to poorer health results for the immunodeficiency patient. This also causes continuous maintenance problems for clinical staff. The effectiveness and reliability of current solutions is questioned by stakeholders, such as the problem of poor cap fit leading to abandoned or failed treatments. Thus, there is no widely available solution for CIA that is both comfortable and minimizes clinical time. CIPN is a widely reported side effect of many chemotherapy treatments, which results in loss of sensory and motor control in the periphery, except for chronic pain. CIPN results in varying degrees of dysfunction in patients and may result in termination or reduced administration of chemotherapy treatment plans, which may increase the incidence and mortality of cancer. Up to 68% of chemotherapy patients report to have CIPN. The additional medical system cost burden for patients with CIPN is estimated to exceed $ 17,000 per patient. The mechanism of CIPN production is not clearly understood, but cytotoxicity caused by frequently used chemotherapeutics (e.g., paclitaxel) is known to cause damage to long myelin fibers in the peripheral pathway, leading to demyelination.

Solutions to prevent CIPN are not in widespread clinical use, but several solutions are recorded in the literature, including the use of cryogenic techniques as used in CIA prevention (e.g. WO2014120090 A1) and the use of compositions or other medical methods that attempt to prevent or reverse CIPN by means of chemical processes. However, there is currently no solution widely available to patients or clinicians to prevent CIPN production.

CII is caused by chemotherapeutics interacting with the male and female reproductive systems, resulting in premature ovarian failure and infertility in female patients, and a reduction or cessation of sperm production in men. While the exact overall prevalence of CII is unknown, the risk of fertility-related side effects of chemotherapy is one consideration in all male and female cancer treatments that one wishes to have children after completing their chemotherapy treatments. In some cases, chemotherapy-induced infertility may be irreversible, resulting in higher levels of psychosocial stress and mental health disorders. This global population of patients considered to be at risk of CII is estimated to be about 1 million patients per year.

There is no widely used or well proven solution to prevent CII in male patients. In female patients, several clinical trials have analyzed the effect of gonadotrophin releasing hormone agonists (GnRHa) in maintaining ovarian function in breast cancer patients. Although this approach has been shown to successfully slow ovarian function (with the aim of reducing the risk and severity of chemotherapy damage), no overall benefit to fertility has been clinically demonstrated. Furthermore, the likelihood of the effectiveness of this approach for other cancers is not clear. In clinical practice, existing solutions for male patients focus on sperm storage, whereas female patients may perform cryopreservation of ovarian tissue via surgical procedures (applicable only to pediatric and young adult patients), in vitro fertilization, or intrauterine insemination. In both cases, current treatment options are highly expensive, with 64% of male patient reports spending greater than or equal to $15,000, while female patients can expect a cost range between $7,000 and $30,000 per patient.

The object of the present invention is to overcome at least one of the problems mentioned above.

Disclosure of Invention

Chemotherapy-induced side effects in disease-free tissues are caused by the accidental destruction of rapidly dividing healthy cells by chemotherapeutic agents. For example, CIA is caused by accidental destruction of rapidly dividing hair cells by chemotherapeutic drugs. The exact pharmacological mechanism of this action is not well understood. Thus, most efforts to prevent hair loss during chemotherapy have surrounded preventing or significantly reducing drug delivery and/or drug absorption to hair follicles.

In one aspect, a pneumatic pressure device and method are provided to prevent chemotherapy-induced side effects by vascular compression therapy locally, upstream, or both, thus reducing drug delivery and/or drug absorption by hair follicles.

The method of the claimed invention (topical microvascular compression therapy) involves applying a small amount of pressure (between about 10mmHg and about 200mmHg, preferably between about 15mmHg and about 190mmHg, more preferably between about 20mmHg and about 180mmHg, optionally between about 20mmHg and about 150mmHg, and between about 20mmHg and about 100mmHg, desirably between about 25mmHg and about 75mmHg, and in one aspect between about 40mmHg and about 60 mmHg) to the tissue surface on the target microvascular, thereby causing the local capillaries of the region to collapse and push blood out of the local blood vessels. The pneumatic pressure devices and methods described herein use this effect to inhibit drug delivery to a target tissue by attaching the pneumatic pressure device to the target region of a subject and applying a constant pressure on the surface of the target tissue.

In one aspect, the invention described herein relates to a pneumatic pressure or compression device. The device of the claimed invention (e.g., a pneumatic pressure cap or device) applies a small amount of pressure (between about 20mmHg and about 100mmHg, desirably between about 25mmHg and about 75mmHg, and in one aspect, between about 40mmHg and about 60 mmHg) to the surface above the bone bulge, causing the local capillaries of the region to collapse and push out the blood in the local blood vessels. The devices described herein use this effect to inhibit drug delivery to, for example, hair follicles by attaching a pneumatic pressure device to the head of a subject and applying constant and/or uniform pressure on the surface of the scalp. The devices described herein also use this effect to inhibit drug delivery to external limbs (e.g., fingers and toes) and areas (e.g., vaginal cavity).

There is provided a pneumatic compression device for preventing or treating chemotherapy-induced hair loss in a subject receiving chemotherapy treatment, the device (1) comprising a headgear component (2), a first layer (3), a second layer (4), an outer mesh layer (6), at least one primary balloon (5) and a control element (9), wherein the at least one primary balloon (5) is located between the first layer (3) and the second layer (4) and is configured to be inflated with air or gas at ambient temperature and to apply a compressive pressure to the scalp of the subject when the balloon (5) is inflated.

In one aspect, there is provided a pneumatic pressure device (1) for preventing or treating chemotherapy-induced hair loss in a subject receiving chemotherapy treatment, the device (1) comprising a headgear assembly (2) adapted to fit the device (1) to the head of the subject; the headgear component (2) is connected to the first layer (3), the second layer (4) and at least one primary airbag (5) sandwiched therebetween; at least one primary airbag (5) is attached to the second layer (4) along its inner edge (5 a) and to the first layer (3) along its peripheral surface (5 b) and to the headgear component (2) along its lower edge surface (5 c); wherein the first layer (3) is enclosed with an outer mesh layer (6) attached to the headgear component (2); and wherein at least one primary balloon (5) is configured to be inflated with air or gas at ambient temperature and which applies compressive pressure to the scalp of the subject when the balloon (5) is inflated.

In one aspect, there is provided a pneumatic compression device (1, 100) for preventing or treating chemotherapy-induced alopecia or chemotherapy-induced peripheral neuropathy (CIPN) in a subject receiving chemotherapy treatment, the device (1, 100) comprising: an attachment part (2), a first layer (3) connected to the attachment part (2), at least one main airbag (5); and a fluid inlet (12), wherein the at least one primary balloon (5) is configured to be inflated with a fluid at ambient temperature and which when the balloon (5) is inflated applies a compressive pressure to the untreated region of the subject to minimize blood perfusion to prevent delivery of chemotherapy to the untreated region.

In one aspect, the pneumatic compression device (1, 100) further comprises a control element (9).

A pneumatic compression device (100) is provided for preventing or treating chemotherapy-induced peripheral neuropathy (CIPN) of a hand or foot of a subject receiving chemotherapy treatment, the device (100) comprising an attachment part (2), a first layer (3), at least one primary airbag (5) and a control element (9), wherein the at least one primary airbag (5) is located between the first layer (3) and the hand or foot of the subject and is configured to be inflated with air or gas at ambient temperature and to apply a compression pressure to the hand or foot of the subject when the airbag (5) is inflated.

In one aspect, at least one primary airbag (5) is configured with a plurality of sleeves (108) to accommodate fingers of a subject's hand or toes of a foot.

In one aspect, the at least one primary airbag (5) is configured as a single sleeve that accommodates the entire hand or foot of the subject.

In one aspect, the pneumatic compression device (100) further includes a first securing member (102) to secure the device (100) in place.

In one aspect, the pneumatic compression device (100) further includes a second securing member (103) to secure the device (100) in place.

A pneumatic compression device (200) is provided for preventing or treating chemotherapy-induced infertility (CII) in a subject receiving chemotherapy treatment, the device (200) comprising at least one primary balloon (205), an applicator (202) adapted to receive the at least one primary balloon (205), and a cap (204) configured to receive the at least one primary balloon (205) within the applicator (202) when deflated, wherein the at least one primary balloon (205) located within the applicator (202) is configured to be inflated with air or gas at ambient temperature and to exert a compressive pressure when the balloon (205) is inflated.

In one aspect, the applicator (202) includes an outer shell (210) and an inner shell (212) that combine to form a housing (214) that houses at least one primary airbag (205).

In one aspect, the pneumatic compression device (200) further includes a support member (208) housed inside the applicator (202) and in communication with the cap (204). When the at least one primary airbag inflates, the cap is released from the applicator and pushed upward while being supported by the support member. The support member bisects at least one primary airbag that encloses the support member when inflated.

In one aspect, the cap (204) is reversibly connected to the applicator (202) and is released from the applicator (202) when the at least one primary airbag (205) is inflated.

In one aspect, the cap (204) is secured to the applicator (202) and further includes an aperture (206) through which at least one primary airbag (205) is pushed prior to inflation.

In one aspect, a control element or control system comprises: a pump; at least one vent (12) for accessing an inflow of air or gas and for allowing the air or gas to leave the device; a tactile on/off switch (14).

In one aspect, the at least one primary airbag (5) further comprises a plurality of airbag compartments, each operating independently of the other.

In one aspect, the at least one primary airbag (5) further comprises a plurality of airbag compartments, each of the plurality of airbag compartments being in fluid communication with an airbag compartment juxtaposed thereto.

In one aspect, at least one main bladder (5) or a plurality of bladder compartments is connected to a pump having a two-way valve system to control the inflow and outflow of air or gas.

In one aspect, the device (1, 100, 200) further comprises a pressure sensor. Preferably, the pressure sensor is in communication with at least one primary airbag (5).

In one aspect, the device (1, 100, 200) further comprises a tissue perfusion sensor.

In one aspect, the device (1) further comprises an outer mesh layer (6) surrounding the second layer (4).

In one aspect, the device (1) further comprises an inner membrane (7), the inner membrane (7) forming an inner liner of the device (1), nested between the second layer (4) and the scalp of the subject.

In one aspect, the device (1) further comprises an auxiliary balloon (11), wherein the auxiliary balloon (11) is configured to be attached to the attachment part (2) such that the auxiliary balloon (11) is in contact with the head of the subject.

In one aspect, the device (1) further comprises a first fastening system (16) configured to prevent the outer mesh layer (6) from moving outwardly.

In one aspect, the device (1) further comprises a second fastening system (17) adapted to tighten the attachment part (2) to the head of the subject.

In one aspect, the device (1, 100, 200) applies a compressive pressure between about 30mmHg to about 350mmHg or to about 200mmHg to the scalp of the subject when activated. Preferably, the compression pressure is between about 30mmHg to about 150mmHg or between about 20mmHg and 100 mmHg; desirably between about 25mmHg to about 75 mmHg; and in one aspect between about 40mmHg and about 60 mmHg.

In one aspect, the compression pressure is applied incrementally.

In one aspect, the compression pressure is applied uniformly or non-uniformly.

In one aspect, the attachment part (2) further comprises at least one status indicator light (13).

In one aspect, the device (1) further comprises at least one adjustable strap (10) to secure the device under, around or over the chin of the subject.

In one aspect, there is provided a method for preventing or treating chemotherapy-induced injury to an off-site region of a patient's body, the method comprising: the method includes the steps of applying compression pressure incrementally to an off-site area (e.g., the pneumatic compression device is in situ at the target site; the target site may be a protected tissue site (in the case of the scalp) or vascular structures upstream of the protected tissue (e.g., targeted to uterine arteries supplying female reproductive organs via the vaginal cavity), and adjusting the applied pressure to balance unwanted drug delivery and avoid occlusion and hypoxia injury of tissue at the protected site.

When the pneumatic compression device applies compression pressure incrementally to the occlusion site, the occlusion site should begin to become partially occluded as the compression system pressure increases incrementally in an electronically or mechanically controlled manner. Depending on the site of application, the applied pressure should reach a peak between 20mmHg and about 200mmHg (preferably between about 20mmHg and about 100 mmHg; desirably between about 25mmHg and about 75 mmHg; and in one aspect between about 40mmHg and about 60 mmHg), so that the user is comfortable and this pressure is maintained while reaching a particular threshold (40 to 60 mmHg) where the local blood flow is reduced by at least 60%. The pressure is maintained in an evenly distributed manner at each point at the occlusion site for a specified period of time related to the half-life of the drug being used to treat the patient, which period of time is electronically or mechanically controlled by the control system. When the pressure peaks, the local blood vessels and microvasculature are almost completely occluded at the occlusion site. Such occlusion reduces or avoids drug delivery to the protected site via the vasculature, ultimately preventing side effects at the protected site. After a specified period of time of applied pressure has elapsed, the pressure is slowly reduced in an electronically or mechanically controlled manner by the control system so as to avoid abrupt reperfusion of the tissue.

The pneumatic compression device will operate for a predetermined period of time based on the half-life of the drug intervention being used.

At expiration time, the pneumatic compression device begins to decrement the applied pressure to allow a safe incremental increase in blood perfusion in the site of action, avoiding reperfusion injury at both the occlusion and the protected site.

At expiration time, the pneumatic compression device begins to decrease the applied pressure in a pulsating manner, thereby significantly decreasing the pressure over a period of 5 seconds, followed by a further period of 5 seconds, followed by another brief period of decreasing pressure, and so forth. In this aspect, safe ascending of blood perfusion in the site of action is allowed, while also increasing blood flow to drive toxins away from the site.

In one aspect, the decrease in perfusion at the target site and the application site is monitored by sensing one of the following parameters: spO2, red blood cell count, hemoglobin concentration.

In one aspect, the compressive force is modified based on the sensed parameter such that a desired amount of compressive force is applied independent of the user.

In one aspect, the device further comprises a foam layer inserted within one or more of the balloon or balloons. The foam is a low density polymeric material such as a low density polyurethane. In this aspect, the pumps connected to the air inlets are connected in opposite polarity so that air is drawn from the air bags. The pump draws fluid (and thus pressure) incrementally, creating a vacuum inside the balloon. This causes the outer first layer and the air bladder to collapse on the foam layer, causing the foam layer to compress. When in a compressed state, the foam layer applies a reactive force through the balloon into the scalp, foot, hand or cavity, creating the level of compression necessary to constrict blood flow.

In one aspect, the fastening system or adjustment component may be used with a greater force to tighten the device against the surface of the scalp, foot or hand. By means of the drawstring mechanism against the scalp/foot/watch face tightening device, the pressure level required for the therapeutic effect is achieved.

In one aspect, a fluid or solid in viscous form at ambient pressure but in solid form at a pressure below atmospheric pressure is inserted into one or more of the balloon or balloons. In this aspect, the pumps connected to the air inlets are connected in opposite polarity so that air is drawn from the bladder and a vacuum is created inside the bladder. As the pressure within the balloon decreases, the substrate hardens, creating a modifiable compressive force against the tissue (scalp, foot, hand, or within the cavity).

In one aspect, the inflated balloon or balloons are inflated using an air inlet to a predetermined pressure level below the target therapeutic pressure level. Compression pressure is applied to the balloon using a fastening system or adjustment means (e.g., a pull cord or hook and grommet strap) to reduce the volume of the balloon in a modifiable manner. This decrease in balloon volume causes an increase in the internal pressure of the balloon, resulting in a modifiable pressure level being applied to the tissue (scalp, foot, hand or cavity) as a target therapeutic range.

In one aspect, the bladder or bladders are provided at a predetermined pressure level and are not modified by the air inlet.

In one aspect, there is provided a method for preventing or treating chemotherapy-induced alopecia in a subject receiving chemotherapy treatment, the method comprising the steps of:

fitting the pneumatic compression device (1) described above to a subject; and

A switch (14) at the rear of the attachment member (2) is activated to initiate inflation of the at least one primary airbag (5) within a specified time.

In one aspect, when the switch (14) is activated, the device inflates and applies increasing pressure to the scalp of the user, as described above. The device uniformly maintains pressure on the scalp surface for a preset period of time. When this time period is completed, the device deflates the balloon in the device in a controlled and decreasing manner predetermined in advance, which avoids any reperfusion injury to the user.

In one aspect, the method further comprises tightening the device (1) to the scalp of the subject by activating the first fastening system 16.

In one aspect, the method further comprises tightening the pneumatic compression device (1) to the scalp of the subject by activating the second fastening system 17.

In one aspect, the method further includes securing the adjustable strap (10) under the chin of the subject.

In one aspect, when the time period is complete and the balloon is deflated, the user can remove the device by loosening the fastening system.

In one aspect, there is provided a method for preventing or treating chemotherapy-induced peripheral neuropathy in a subject receiving chemotherapy treatment, the method comprising the steps of:

fitting the pneumatic compression device (100) described above to a subject; and

A switch on the control element is activated to initiate inflation of the at least one primary airbag 5 for a specified time.

In one aspect, the method further comprises tightening the device (100) to the subject's foot or hand by activating the first securing member or the second securing member or a combination of both.

In one aspect, there is provided a method for preventing or treating chemotherapy-induced infertility in a subject receiving chemotherapy treatment, the method comprising the steps of:

fitting the pneumatic compression device (200) described above to a subject; and

A switch on the control element is activated to initiate inflation of the at least one primary airbag (205) for a specified time.

In one aspect, there is provided a method of controlling delivery of a drug to a target site on a body via a blood vessel, the method comprising:

Mechanically compressing skin/surface tissue at the target tissue site with a predetermined compression force to occlude the upstream blood vessel;

maintaining the compressive force for a predetermined period of time (such that the drug circulating through the vascular system does not reach the target site); and

The compressive force applied to the tissue at the target site is released at a predetermined rate and in a predetermined geometric pattern (releasing the compressive force includes relieving the mechanical compressive force so that long-term tissue damage and ischemia reperfusion injury can be avoided).

When the blood vessel is occluded, this causes occlusion of local microvasculature and superficial arteries, where the possibility of delivering the drug at the target tissue site or at an organ site downstream of the target tissue site is limited.

In one aspect, when a compressive force is applied to a tissue site upstream of the intended site of action. This means that a compressive pressure is applied to the target vessel at a point different from the intended site of protective action.

In one aspect, a compressive force of about 20mmHg to about 100mmHg is applied to the skin/surface tissue at the target site.

In one aspect, the applied compressive force is configured to mechanically occlude the microvasculature proximate the surface of the tissue and the local arterial supply vessel.

In one aspect, the compressive pressure is applied uniformly across the tissue site to be treated.

In one aspect, the compressive force is maintained for a period of time between 30 minutes and 7 hours.

In one aspect, compressive forces are applied at different regions of tissue such that larger vessels can withstand larger levels of compression.

In one aspect, the compressive force is applied in a pulsating manner.

In one aspect, there is provided a method of controlling drug delivery to a target site on a body, followed by reactivating blood flow for a period of time to ensure long-term tissue viability, the method comprising:

mechanically compressing skin/surface tissue at a target site with a predetermined compression force to cause occlusion of local microvasculature, wherein the likelihood of delivering the drug is limited;

maintaining the microvascular occlusion for a predetermined period of time such that the drug circulating through the vascular system does not reach the target site;

releasing the occlusion in a controlled manner at a predetermined rate and in a predetermined geometric pattern such that long-term tissue damage and ischemia reperfusion injury can be avoided;

sensing a physiological parameter;

adjusting a mechanical compression applied to the tissue site based on the sensed physiological parameter; and

Compressive forces are applied to the skin tissue in a pulsatile manner to promote blood flow, allowing the removal of the spent agent from the local vascular structure.

In one aspect, the sensed physiological parameter is blood perfusion in the treated tissue site. Blood perfusion in tissue is typically measured by Magnetic Resonance Imaging (MRI), positron Emission Tomography (PET), and laser doppler methods. MRI is a non-invasive technique that directly measures blood flow by using arterial blood as an endogenous tracer. PET scanning requires the introduction of a radioactive tracer into the blood supply. Laser doppler flow measurement (LDF) is an established surface technique for measuring red blood cell movement at a tissue surface in real time. LDF and Laser Doppler Imaging (LDI) work by illuminating tissue with laser light. Perfusion measurements are derived from the product of the average velocity and the measured concentration of red blood cells within the volume of tissue. Perfusion is measured at the tissue surface and is only given as a relative value.

Definition of the definition

In the specification, the term "health" is understood to mean a condition in which an individual or patient is free of an underlying medical condition, infection, inflammatory response, condition, or otherwise occurring.

In the specification, the term "cancer" is understood to mean a cancer selected from the group comprising: lymph node negative, ER positive breast cancer; early stage lymph node positive breast cancer; multiple myeloma, prostate cancer, glioblastoma, lymphoma, fibrosarcoma; myxosarcoma; liposarcoma; chondrosarcoma; osteogenic sarcomas; chordoma; hemangiosarcoma; endothelial sarcoma; lymphangiosarcoma; lymphatic endothelial sarcoma; synovial tumor; mesothelioma; ewing's tumor; leiomyosarcoma; rhabdomyosarcoma; colon cancer; pancreatic cancer; breast cancer; ovarian cancer; squamous cell carcinoma; basal cell carcinoma; adenocarcinomas; sweat gland cancer; sebaceous gland cancer; papillary carcinoma; papillary adenocarcinoma; cystic adenocarcinoma; medullary carcinoma; bronchial carcinoma; renal cell carcinoma; liver cancer; bile duct cancer; choriocarcinoma; seminoma; embryo cancer; wilms' tumor; cervical cancer; uterine cancer; testicular tumor; lung cancer; small cell lung cancer; bladder cancer; epithelial cancer; glioma; astrocytoma; medulloblastoma; craniopharyngeal pipe tumor; ventricular tube membranoma; pineal tumor; angioblastoma; auditory neuroma; oligodendrogliomas; meningioma; melanoma; retinoblastoma; and leukemia. Also included are cancer metastasis selected from the group comprising: bone cancer metastasis; lung cancer metastasis; liver cancer metastasis; bone marrow cancer metastasis; breast cancer metastasis and brain cancer metastasis.

In the specification, the term "individual", "subject" or "patient" is understood to mean an animal, which includes all mammals, such as humans, primates, non-human primates, farm animals (e.g., pigs, horses, goats, sheep, cows (including bulls, calves, heifers, etc.), donkeys, reindeer, etc.), veterinary mammals (e.g., dogs, cats, rabbits, hamsters, guinea pigs, mice, rats, ferrets, etc.), and confined mammals (e.g., lions, tigers, elephants, zebras, giraffes, pandas, rhinoceros, river horses, etc.), as well as other mammals and higher mammals to which the invention is viable.

In the specification, the term "treatment" is understood to mean preventing, limiting and slowing, stopping or reversing the progression or severity of, for example, chemotherapy-induced alopecia (CIA), chemotherapy-induced peripheral neuropathy (CIPN) and chemotherapy-induced infertility (CII).

In the specification, the term "vasoconstriction" is understood to mean a narrowing of blood vessels caused by the contraction of the muscle walls of blood vessels (in particular, the aorta and the small arterioles), thereby reducing the blood flow in those blood vessels to reduce the delivery of chemotherapeutic agents, for example, to the scalp to limit hair loss. The main arteries of the scalp are the supratrochlear artery, the supraorbital artery, the superficial temporal artery and the occipital artery; while the major veins are the superficial temporal vein, the posterior auricular vein and the occipital vein. The main arteries of the limb are radial artery, ulna artery, brachial artery, dorsum of foot artery, anterior tibial artery, lateral calcaneus artery, medial calcaneus artery, lateral plantar artery and medial plantar artery. The main arteries of the bone pelvis are the superior vaginal artery, the uterine artery and the ovarian artery.

In the specification, the term "balloon" is understood to mean a sealed bag that can be filled with a fluid and configured to withstand pressures up to 500mmHg in the context of the claimed inventive device.

In the specification, the term "fluid" is understood to mean a substance that does not have a fixed shape, flows easily, and generates external pressure easily. Examples of fluids include gases, air, or liquids.

In the specification, the term "shell" is understood to mean a shell or protective housing that may be composed of a hard, soft or compliant (malleable) material. Examples of hard materials include hard plastics, metallic (e.g., aluminum, stainless steel) fiberglass, carbon fiber, graphene, acrylonitrile Butadiene Styrene (ABS), polylactic acid (PLA), and the like. Examples of soft materials include cotton, hemp, silk, foam, polyurethane (PU) gel/foam, silicone, latex, polyvinyl chloride (PVC), polyethylene (PE), polyester, bamboo fabric, and the like. Examples of compliant materials include rubber, memory foam, and the like. Other components that may be embedded with the soft or compliant materials mentioned above include antimicrobial agents such as silver, copper, zinc, and the like.

In the present description, the term "pressure sensor" is understood to mean a device for measuring the fluid pressure inside the balloon. Typically, the sensor includes a resistive, capacitive, or inductive sensing element, and may measure 0 to about 100kPa; preferably about 0 to about 80kPa; more preferably from about 0 to about 50 or about 60kPa; and desirably from about 0 to about 40 kPa.

In the specification, the term "tissue perfusion sensor" is understood to mean a device that measures blood perfusion levels in tissue (e.g. scalp tissue). Typically, the sensor comprises a non-invasive convective blood perfusion probe that adapts to the shape of the area being treated. For example, for scalp compression, the sensor is circular in shape and rests on the scalp surface. Perfusion measurements are derived from the product of the average velocity and the measured concentration of red blood cells within the volume of tissue. The measurement range is typically about 1, 2, 3, 4 or 5mm of tissue depth below the probe.

In the specification, the term "pneumatic" is understood to mean the use of gas or air operating under pressure.

In the specification, the term "ambient temperature" is understood to mean the average air temperature around something (e.g., an individual). Typically, this means "room temperature", which means a dry, clean, well ventilated area at temperatures between 15 ℃ to 25 ℃ (59°f to 77°f) or up to 30 ℃ depending on the climatic conditions.

In the specification, the term "cavity" is understood to mean nasal, oral and pelvic cavities (including genital organs, vaginal cavities, bladder, distal ureters, proximal urethra, distal sigmoid colon, rectum and anal canal). In women, the uterus, fallopian tubes, ovaries and (upper) vagina occupy the area between other viscera.

In the specification, the term "untreated region" is understood to mean a non-target region of the body that is not affected by the cancer being treated.

In the specification, the terms "control element" and "control system" are interchangeable and should be understood as generally housing a pump, at least one air or gas vent for accessing an air or gas inflow and for allowing an air or gas outflow, at least one pressure sensor and a tactile on/off switch. The at least one pressure sensor may also be located within or on the tissue facing side of the at least one primary balloon and remain connected to the control element/system. The control element or system further comprises control electronics for reading inputs from the pump and the at least one air pressure sensor. The pump is powered by a battery housed within the control element/system.

Drawings

The invention will be more clearly understood by the following description of an embodiment thereof, given by way of example only, with reference to the accompanying drawings, in which: -

Fig. 1 illustrates a perspective view of a pneumatic compression device of the claimed invention.

Fig. 2 illustrates the pneumatic compression device of fig. 1 with a cutaway portion of the layers of the display device.

Fig. 3A illustrates the control element of the claimed invention for use with the pneumatic compression device of fig. 1, while fig. 3B illustrates the control element attached to the rear of the device of the claimed invention. When the scalp compression device of fig. 1 is in use, wherein (a) the device is placed on the patient's head, (b) the dial of the back of the device is rotated to tighten and align the device on the patient's head, and (c) the motorized dial of the front of the pressure sensor activation device is used to progressively apply and control pressure in the device to produce the desired compression.

Fig. 4 illustrates a rear perspective view of the device described above, with the auxiliary balloon indicated by the dashed lines.

Fig. 5 illustrates the device of the claimed invention used on the hands of a subject receiving chemotherapy treatment.

Fig. 6 illustrates the device of fig. 5 having an outer layer in cross-section, revealing the underlying primary airbag.

Fig. 7 illustrates the device of fig. 5 and 6 in cross-section.

Figure 8 illustrates the device of the claimed invention for use on the foot of a subject receiving chemotherapy treatment.

Fig. 9 illustrates the device of fig. 8 having an outer layer in cross-section, revealing the underlying primary airbag.

FIG. 10 illustrates a device of the claimed invention for use in a lumen of a subject receiving chemotherapy treatment, wherein (A) the device is shown in situ but undeployed; (B) displaying the device during deployment; and (C) shows the fully deployed device, while (D) shows the fully deployed device in the form of a cross-section of (C), revealing the internal elements of the device.

FIG. 11 illustrates a device of the claimed invention for use in a lumen of a subject receiving chemotherapy treatment, wherein (A) the device is shown in situ but undeployed; (B) displaying the device during deployment; (C) Displaying the device in cross-sectional form of (B), thereby revealing the internal elements of the device; and (D) shows the device fully deployed.

Fig. 12 illustrates a graph showing the reduction in tissue perfusion compared to that at baseline of the target site (in the case of scalp) of eight human volunteers when different compression pressure levels were applied using the device of the claimed invention. Tissue perfusion was measured in a relative perfusion unit as provided by Moor instrument laser doppler monitoring.

Detailed Description

Local microvascular compression therapy is used to prevent CIA, CIN, CII and other drug side effects (e.g., skin dryness and mucositis). The pneumatic compression device of the claimed invention modulates local drug delivery to protect non-target tissues. The pneumatic compression device applies tissue and/or vascular compression in the range of 20mmHg to 200mmHg (preferably about 20mmHg to about 100 mmHg) from pneumatic compression against unbroken (unpunctured) skin or internal structures (e.g., within the vaginal cavity) to occlude the local blood vessel, thereby causing, in part or in whole, reduced blood perfusion at the protected site and thus reduced drug delivery at the site of action (or protected tissue site). This modulation of local drug delivery reduces or eliminates undesirable side effects at the protected tissue site caused by drugs in the circulatory system.

First, the pneumatic compression device will exert pressure over a large area to reduce blood pre-fusion to the protected tissue. This large area approach allows for lower pressure levels (20 to 100 mmHg) than conventional tourniquet devices (which exert high pressure on small areas). This larger pressure footprint allows for more patient comfort during treatment. Second, the applied pressure is adjusted during treatment to reduce or avoid perfusion-related damage to the tissue at the occlusion site or protected site. The decrease in pressure after treatment will also be controlled to avoid reperfusion injury.

The above pneumatic compression device can significantly reduce non-target drug-related damage to the skin, peripheral nerve endings, ovaries or bladder, and other tissues and organs.

The present invention provides a pneumatic compression device designed to apply uniform or non-uniform incremental pressure to an area of a subject for therapeutic purposes to prevent damage caused by a chemotherapeutic agent. Prior to chemotherapy infusion, the device may be fitted into the subject's head, foot, hand or cavity, secured in place (where appropriate), and then activated. The device may be used with any size or shape of head, foot, hand or cavity, which allows it to be used for all ages (from infant to adult), providing flexibility and ease of use. The internal balloon mechanism is incrementally inflated with a fluid at room temperature to apply (uniform/non-uniform) pressure to a region of interest, such as the scalp. With this level of therapeutic pressure applied before, during, and after chemotherapy treatment, the device causes local vasoconstriction of the blood vessel, thereby reducing tissue perfusion in the area of interest, and thus preventing drug delivery to, for example, hair follicles or other non-target areas.

Referring now to the drawings, wherein FIG. 1 illustrates a general embodiment of a pneumatic compression device of the present invention for use with a subject's scalp. In particular, fig. 1 illustrates a perspective view of a pneumatic compression device of the present invention fitted to a subject's head and generally indicated by reference numeral 1. The device 1 of the illustrated embodiment comprises an attachment part 2 adapted to fit the device 1 to the head of a subject. The attachment part 2 is connected to the first layer 3, the second layer 4 (see fig. 2) and at least one primary airbag 5 (see fig. 2) sandwiched therebetween. The attachment means 2 act as anchors for other elements of the device 1. At least one primary airbag 5 is attached to the second layer 4 along its inner edge 5a and to the first layer 3 along its peripheral surface 5b and to the attachment member 2 along its lower edge surface 5 c. At least one primary airbag 5 is inflated with a fluid, preferably air or gas (which is preferred at room temperature). The first layer 3 is typically covered with an outer mesh layer 6, which is also attached to the attachment part 2. The attachment part 2 is typically rigid.

When inflated, at least one primary balloon 5 expands and applies pressure to the head Pi Shi, as the balloon 5 may expand only toward the scalp. The outer mesh layer 6 stops any outward expansion of the device 1 away from the scalp. One of the functions of the outer mesh layer 6 is to restrain the main air bag 5 so that the air pressure inside the main air bag 5 is applied to the scalp. If a series of interconnected main balloons 5 or a series of balloon compartments are used, different amounts of pressure may be applied to the same or different areas of the scalp.

The device 1 further comprises an inner membrane 7. The inner membrane 7 ensures that the device 1 is a comfortable fitting on the subject. In one aspect, the inner membrane 7 extends in conjunction with the attachment member 2, i.e. circumferentially around the head of the subject. The inner membrane 7 forms a seal around the scalp of the subject. In one aspect, the inner membrane 7 forms the innermost liner of the device 1 and is nested between the second layer 4 and the head of the subject, thereby encapsulating substantially the entire area of the scalp when the device 1 is assembled to the subject. The inner membrane 7 is typically a soft or malleable (compliant) material that is comfortable to the wearer.

The inflatable at least one primary airbag 5 is configured to be connected to a pump that inflates the at least one primary airbag 5 with air or gas when the device 1 is turned on. The pump and any associated electronic control architecture are housed in a detachable control element 9 which is attached in a slot 20 in the attachment part 2 at the rear of the device 1. Thus enabling the at least one primary balloon 5 to exert an increasing compressive force on the head of the subject wearing the device 1, the at least one primary balloon being restrained in place by both the attachment member 2 and the outer mesh layer 6.

In use, the device 1 is positioned on the scalp of a subject and may be secured in place by a plurality of adjustable straps 10 attached to the attachment means 2, which are anchored on, around or under the chin of the subject (see figure 2). In one aspect, the adjustable strap may be replaced with a pull cord system attached to the side of the device 1. In one aspect, the device 1 is secured to the scalp by an auxiliary balloon 11 that is positioned on the inner surface of the attachment member 2 such that it is in contact with the forehead, temple and nape of the subject wearing the device 1 (see fig. 1, 4). When a fluid (preferably air or gas) is provided to the auxiliary balloon 11, it inflates to create a seal against the forehead, temple and base or nape of the subject's head, thereby securing the device 1 in place and creating a seal when at least one primary balloon 5 is filled with air or gas and therapeutic compression is applied to the scalp.

Turning now to fig. 3A and 3B, the control element 9 is shown separated (fig. 3A) and in situ within the slot 20 (fig. 3B). The control element 9 generally houses a pump, at least one air or vent 12 for the inflow of air or gas and for the outflow of air or gas back, at least one pressure sensor and a tactile on/off switch 14. The at least one pressure sensor may also be located within the at least one primary balloon 5 or on the scalp-facing side of the at least one primary balloon 5 and remain connected to the control element 9. This control element 9 further comprises control electronics for reading inputs from the pump and the at least one air pressure sensor. The pump is powered by a battery housed within the control element 9 of the device 1. The battery may be a rechargeable battery or a disposable battery.

The headband component 2 also incorporates at least one status indicator light 13 (see fig. 1) which communicates with the control element 9. The status indicator light 13 communicates with the control element 9 via a wired connection through the attachment part 2 and into the control element 9. At least one indicator light 13 is used to indicate whether the device 1 is on and running, off or malfunctioning.

Any incremental change in pressure is measured by at least one air pressure sensor connected to at least one primary air bladder 5. The compressive pressure applied to the scalp by device 1 is in the range of about 20mmHg to about 350mmHg or to about 200 mmHg; but preferably between about 20mmHg to about 150mmHg, more preferably between about 20mmHg and about 100 mmHg; desirably between about 25mmHg and about 75 mmHg. Typically, the applied compression pressure is between about 40mmHg and 60 mmHg. When activated, the pump housed within the device 1 inflates at least one primary airbag 5 to a specified compression pressure, thus functioning like a pneumatic device. This compressive pressure causes local vasoconstriction and a reduction in the level of dermal tissue perfusion, which prevents drug delivery to the hair follicle. When the chemotherapy treatment is completed, the device 1 is deflated using a valve system or using a pump of opposite polarity.

In one aspect, the device 1 includes a number of air pressure sensors located at a number of points within the device 1. When the pressure reaches a certain threshold (e.g., a low (e.g., 30mmHg or 40mmHg pressure) or high (e.g., between about 60mmHg and about 200mmHg pressure), at one or more of the points measured by the pressure sensor, pumps are activated as needed to pump more air (fluid) into the at least one primary balloon 5 resulting in more head skin compression or to remove air from the at least one primary balloon 5 resulting in less scalp compression.

In one aspect, a tissue perfusion sensor (e.g., a laser doppler blood flow sensor) is incorporated into or on the scalp-facing surface of the second layer 4 or attachment member 2. The tissue perfusion sensor analyzes the blood flow level in the compressed scalp tissue. This information is used to activate the pump to increase or decrease the pressure in at least one of the primary airbag 5 or the airbag compartment using an embedded software system and controlled by the architecture of the control element 9.

Tissue perfusion sensors may be incorporated in several ways. In one aspect, the tissue perfusion sensor is incorporated into the hollow in the material comprising the second layer 4 such that the sensor is in contact with the scalp of the subject. In one aspect, there are at least two tissue perfusion sensors incorporated within the attachment component 2 such that the positioning of the tissue perfusion sensors corresponds to the temple regions on each side of the user's head. In another aspect, there are a plurality of tissue perfusion sensors configured to be patterned around the scalp by being adhered to at least one primary balloon 5 or within at least one primary balloon 5, or within or on each polarity balloon compartment in a specific pattern, thereby ensuring that the perfusion sensors are dispersed around and cover the scalp area. In another aspect, a plurality of tissue perfusion sensors are integrated into the inner shell 4 such that they are in direct contact with the scalp of the subject. The use of a single, two or more tissue perfusion sensors permits the user to determine blood flow at different points of the scalp of the subject, and to determine how much pressure is needed to constrict the blood vessel to prevent blood flow at that point in the scalp.

In one placeIn aspects, the sensor (air pressure, tissue perfusion) and pump further include a power source, circuitry to measure its resistance, and means to control the sensor and pump and record the readings. In other aspects of any of the embodiments described herein, the air pressure sensor, the tissue perfusion sensor, and the pump may further comprise: wireless technology, which is used to exchange data between the sensor and the pump and the control element 9 of the device 1 within a short distance using, for example, short wavelength UHF radio waves (for example, ) The method comprises the steps of carrying out a first treatment on the surface of the Other wireless data transmission methods, such as wireless mesh networks targeting battery-powered devices in wireless control and monitoring applications (e.g.)>) The method comprises the steps of carrying out a first treatment on the surface of the Local area networking and internet access of devices (e.g.)>) The method comprises the steps of carrying out a first treatment on the surface of the And other wireless communication protocols using mesh networks that use low energy radio waves to communicate from home appliance to home appliance (e.g.)>). Typically, a remote application may be used on device 1 or with device 1 to record readings from the air pressure sensor, tissue perfusion sensor, and/or pump. In this way, the user can remotely control the inflation of the at least one primary 5, secondary 11 and balloon compartments. Alternatively, the device 1 itself controls the inflation pressure based on feedback from the sensor to the control element 9. The sensors (air pressure and tissue perfusion) and the pump may also be physically connected to the control element 9 by wiring.

At the rear of the device 1 there is a first fastening system 16 configured to tighten the outer mesh layer 6 in order to fasten the device 1 to the head of the wearer (see fig. 3B). In use and to provide initial fastening of the device 1 to the head of a subject, the subject twists the first fastening system 16 in one direction (e.g., in a clockwise direction) to tighten the outer mesh layer 6 and twists the first fastening system 16 in the opposite direction (e.g., in a counter-clockwise direction) to loosen the outer mesh layer 6.

In a similar manner, the second fastening system 17 is used to tighten the attachment part 2 to the temple, forehead and nape of the subject. This means that the subject can place the device 1 in a comfortable position, first by twisting the first fastening system 16 and/or the second fastening system 17 to mechanically tighten the headgear component 2 to ensure that the device 1 is properly positioned for the subject, and then activating the on/off switch 14 to fill the auxiliary airbag 11 and create a seal around the forehead, temple, and lower region of the subject's head to hold the device 1 in place.

The first fastening system 16 and the second fastening system 17 may be adjusted manually by a user or electronically by the architecture of the control element 9. The first fastening system 16 and the second fastening system 17 are generally motors with fastening elements of the torsion systems 16, 17 in their construction. It should be noted that the device 1 can be used without the first fastening system 16 and the second fastening system 17; or in the case of engagement of only one of the first fastening system 16 and the second fastening system 17.

Referring now to the drawings, wherein fig. 5-9 illustrate a general embodiment of a pneumatic compression device of the present invention for use with a subject's hand or foot. Where elements of each embodiment are shared, the same reference numerals are used. Specifically, FIG. 5 illustrates a perspective view of the pneumatic compression device of the present invention fitted to a subject's hand and generally indicated by reference numeral 100. The device 100 comprises a first layer 3 in the shape of a glove or mitt that can fit on the hand of a user. The first layer 3 is secured to the wearer using an attachment means 2 which tightens the device 100 against the wearer. Furthermore, the first fixing element 102 and the second fixing element 103 may also be used to fix the first layer 3 in place around the user's finger, respectively. At least one primary airbag 5 connected by a single fluid inlet 12 is attached to the inner surface of the first layer 3 (see fig. 6 and 7). At least one primary airbag 5 is arranged such that each point on the skin of the wearer's finger, wrist and forearm is in contact with the primary airbag 5. The fluid inlet 12 is then connected to a pump (not shown) that is electrically coupled to the pressure regulation system/sensor. The pump drives fluid (e.g., air, oxygen, water) into the fluid inlet 12 and then into the at least one primary airbag 5. The primary airbag may be arranged with a plurality of sleeves 108 that receive the fingers and thumb of a user's hand (see fig. 6 and 7). Alternatively, a mesh of primary air bags 5 is provided which can be brought into contact with the individual fingers and thumbs of the user. At least one primary airbag 5 inflates and applies compressive pressure incrementally to the wearer's skin. The device 100 may be programmed to remain inflated until the pressure reduces the user's skin perfusion and prevents drug delivery. When the treatment is completed, the device 100 is deflated using the pump and fluid outlet (or inverted fluid inlet (12)).

In one aspect, one or more perfusion sensors are placed on the surface of the plurality of sleeves 108 forming at least one primary bladder 5 that is in contact with the skin of the wearer. The input from the perfusion sensor may be used to adjust the level of compressive pressure applied to the wearer by the at least one bladder 5.

Referring now to fig. 8, a general embodiment of a pneumatic compression device of the present invention for use with a subject's foot is illustrated. Where elements of each embodiment are shared, the same reference numerals are used. Specifically, fig. 8 illustrates a perspective view of the pneumatic compression device of the present invention fitted to a subject's foot and generally indicated by reference numeral 100. The first layer 3 is formed in the shape of a sock that can be fitted over the foot of a user. In this embodiment, at least one primary airbag 5 is arranged such that each skin surface on the user's toes, feet and ankles is in contact with at least one primary airbag 5. In one aspect, a web of primary air bags 5 is provided that can be brought into contact with the individual toes and the user's feet and ankles. At least one primary airbag 5 connected by a single fluid inlet 12 is attached to the inner surface of the first layer 3 (see fig. 9).

A sterile contact layer is placed between at least one primary balloon 5 and the skin surface of the wearer. Such sterile contact layers are typically constructed of biocompatible, sterilizable plastics (e.g., polyethylene). The first layer 3 is secured to the wearer using an attachment means 2 which tightens the device 100 against the wearer. In addition, the first and second securing members 102, 103, respectively, may also be used to secure the first layer 3 in place around the user's foot. The fluid inlet 12 is then connected to a pump (not shown) that is electrically coupled to a pressure regulation system/sensor, i.e., a control system (as described for the device 1). The pump drives fluid (e.g., air, oxygen, water) into the fluid inlet 12 and then into the at least one primary airbag 5. A mesh of main air bags 5 is provided which can be brought into contact with the individual toes, heels, soles and ankles of the user. At least one primary airbag 5 inflates and applies compressive pressure incrementally to the wearer's skin. The device 100 may be programmed to remain inflated until the pressure reduces the user's skin perfusion and prevents drug delivery. When the treatment is completed, the device 100 is deflated using the pump and fluid outlet (or inverted fluid inlet (12)).

Referring now to fig. 10 and 11, a general embodiment of a pneumatic compression device of the present invention for use with a subject's lumen is illustrated. Where elements of each embodiment are shared, the same reference numerals are used. Specifically, fig. 10A illustrates a perspective view of the pneumatic compression device of the present invention in situ within a vaginal cavity of a subject and generally designated by reference numeral 200. The device 200 includes at least one primary airbag 205 and an applicator 202 including an outer housing 210 and an inner housing 212 forming a housing 214 that houses the at least one primary airbag 205, and a cap 204 that rests atop the applicator 202. The applicator 202 delivers at least one primary balloon 205 to a tissue target while in an internal cavity (e.g., in a vaginal cavity according to fig. 10 and 11). When properly placed in the cavity by the user, at least one primary balloon 205 is pushed from housing 214 into the confines of the cavity by support axis 208 (see fig. 10D). Cap 204 is in communication with support axis 208 and is disengaged from the end of applicator 202 when activated (see fig. 10B and 10D). When the at least one primary balloon 205 is outside the housing 214 of the applicator 202, the at least one primary balloon 205 or multiple primary balloons 205 are inflated through the inlet 12 via the control system using a pump (as described above for devices 1 and 100), such that the at least one primary balloon 205 or multiple primary balloons 205 expand to apply compression to the walls of the lumen (see fig. 10C and 10D).

At least one primary airbag 205 inflates and applies compressive pressure incrementally to the wearer's skin. The device 200 may be programmed to remain inflated until the pressure reduces the user's tissue perfusion and prevents drug delivery. When the treatment is completed, the device 200 is deflated using the pump and fluid outlet (or inverted fluid inlet (12)).

In one aspect, one or more perfusion sensors are placed on the surface of at least one primary balloon 205 or multiple primary balloons 205 that are in contact with the tissue of the lumen. The input from the perfusion sensor may be used to adjust the level of compression pressure applied to the user by the at least one primary bladder 205 or multiple primary bladders 205.

Referring now in greater detail to fig. 11, cap 204 resting atop applicator 202 further includes aperture 206. The aperture 206 is configured to direct at least one primary airbag 205 from the housing 214 to the cavity. When the user acts on the support axis 208, at least one primary balloon 205 exits the aperture 206 and enters the confines of the cavity (see fig. 11B). Cap 204 is disengaged from support axis 208 and remains in communication with the top of applicator 202. The support axis 208 remains engaged with the at least one primary airbag 205 (see fig. 11C). When the at least one primary balloon 205 is outside the housing 214 of the applicator 202, the at least one primary balloon 205 or multiple primary balloons 205 are inflated through the inlet 12 via the control system using a pump (as described above for devices 1 and 100), such that the at least one primary balloon 205 or multiple primary balloons 205 expand to apply compression to the walls of the lumen (see fig. 11D).

Materials and methods

The device 1, 100, 200 is operated by a wearer in a clinical environment, as set forth below.

1. The device 1, 100, 200 is provided in a loose, unsecured manner.

2.For scalpThe clinician or user loosely places the device 1 on the subject's head and ties the device 1 in place using the securing mechanism 10 and the auxiliary balloon 11, the first fastening system 16 or the second fastening system 17, or a combination thereof.

3. The device 1 is switched on by pressing a button 14 at the rear of the device 1. The device 1 then starts to inflate and the status light 13 indicates that the device 1 is on and that the at least one primary airbag 5 starts to inflate.

4. When the device 1 reaches the target pressure application, the status light 13 indicates that the device 1 is now in "active" mode. The device 1 will remain active for a pre-programmed period of time.

5.For hands or feetThe clinician or user loosely places the device 100 on the subject's hand or foot and ties the device 100 in place using the first securing member 2, the second securing member 102, or the third securing member 103, or a combination thereof.

6. The device 100 is turned on by pressing a button on a control system that incorporates a pump that is electrically coupled to a pressure regulation system/sensor. The pump then begins to inflate the at least one primary airbag 5 and the status light on the control system indicates that the device 100 is on and that the at least one primary airbag 5 begins to inflate.

7. When the device 100 reaches the target pressure application, the status light indicates that the device 100 is now in an "active" mode. The device 100 will remain active for a pre-programmed period of time.

8.For cavityThe clinician or user places the device 200 within the cavity.

9. The device 200 is turned on by pressing a button on a control system that incorporates a pump that is electrically coupled to a pressure regulation system/sensor. The pump then begins to inflate the at least one primary airbag 205 and the status light on the control system indicates that the device 200 is on and that the at least one primary airbag 205 begins to inflate.

10. When the device 200 reaches the target pressure application, the status light indicates that the device 200 is now in an "active" mode. The device 200 will remain active for a pre-programmed period of time.

11. The clinician may then begin the operation of the chemotherapy infusion process.

12. After completion of the chemotherapy infusion, the patient is free to leave the clinical setting while wearing the device 1, 100, 200.

13. After the active chemotherapy session has ended, the status indicator light will indicate that the treatment is complete. The control element 9 or control system further comprises a timing system which can be set to a specific amount of time for which the device 1, 100, 200 is inflated to apply pressure to the scalp/hands/feet/cavities of the user. The timing system may be set to the amount of time that chemotherapy treatment is administered, or the control element 9 or control system may be connected to the chemotherapy treatment delivery device (physically connected via a plug-and-play wiring set or wirelessly) and reflect the time that treatment will take. When the time period is completed, the user may then press the shut-off button (14) or the shut-off button (14) will automatically disengage by the control element 9 or control system, which triggers the pump to withdraw fluid from at least one main balloon 5, 205 (or from multiple balloon compartments 5, 205) and expel fluid through the vent to slowly release pressure from the device 1, 100, 200.

14. After releasing the pressure, the device 1, 100, 200 completes the shutdown procedure, and the user is then free to relax or remove the device 1, 100, 200 and store it.

15. The user brings the device 1, 100, 200 to the clinic at their next appointment.

Conclusion(s)

The device 1, 100, 200 may be worn for a defined period of time before, during and after chemotherapy treatment. The expected wear time is at most about 30 minutes prior to the chemotherapy infusion, with continued wear during the chemotherapy infusion and for another 60 to 120 minutes, preferably 90 minutes, after the infusion is completed. A key benefit of this solution is that the subject may leave the infusion ward while wearing the device 1, 100, 200, rather than having to spend additional time wearing the device 1, 100, 200 after the infusion center has completed infusion therapy.

The claimed inventive device 1, 100, 200 is an optimal, comfortable and portable solution for preventing hair loss during chemotherapy. The device 1, 100, 200, being designed to fit the existing clinical workflow, avoids the problems of capital costs, infection control and patient discomfort associated with existing products.

The use of the pneumatic balloon in the device 1, 100, 200 is inherently expanded to fill the free space around it. This is a very advantageous feature in the device 1, 100, 200, as it means that given enough spatial expansion, the balloon system will expand to fit any shape of head, hand, foot or cavity, and will apply the same pressure equally to each surface it contacts.

The device 1, 100, 200 regulates drug delivery at a low pressure level at the microvascular level to avoid any problem of lack of blood flow in a large part of the body. This is illustrated in fig. 12, where tissue perfusion at the target site is shown to be significantly reduced from a "baseline" resting state to a lower level when compression is applied using the device 1. This figure shows the average reduction in tissue perfusion at a depth of 1.5mm at the target site (as measured using a laser doppler flow meter) when the device 1 is used in eight healthy human volunteers. Prior art devices use cryogenically induced vasoconstriction and prior compression devices have focused primarily on increasing blood flow.

In the description, the term "include/comprise/include/comprised" or any variant thereof and the term "include/comprised" or any variant thereof are to be regarded as being entirely interchangeable and they should be given as broad an interpretation as possible, and vice versa.

The invention is not limited to the embodiments described above but may be varied in construction and detail.

Claims

1. A pneumatic compression device (1, 100) for preventing or treating chemotherapy-induced alopecia or chemotherapy-induced peripheral neuropathy (CIPN) in a subject receiving chemotherapy treatment, the device (1, 100) comprising: -an attachment part (2), -a first layer (3) connected to the attachment part (2), -at least one primary airbag (5); and a fluid inlet (12), wherein the at least one primary balloon (5) is configured to be inflated with a fluid at ambient temperature and which, when the balloon (5) is inflated, applies a compressive pressure to an untreated region of the subject to minimize blood perfusion to prevent delivery of chemotherapy to the untreated region.

2. The pneumatic compression device (1) according to claim 1, further comprising a second layer (4) and an outer mesh layer (6) surrounding the second layer (4).

3. The pneumatic compression device (1) of claim 1 or claim 2, further comprising an inner membrane (7), the inner membrane (7) forming an inner liner of the device (1), nested between the second layer (4) and the subject's tissue.

4. The pneumatic compression device of any one of the preceding claims, further comprising an auxiliary balloon (11), wherein the auxiliary balloon (11) is configured to be attached to the attachment member (2) such that the auxiliary balloon (11) is in contact with the tissue of the subject.

5. The pneumatic compression device (1) according to any one of the preceding claims, further comprising a first fastening system (16) configured to prevent the outer mesh layer (6) from moving outwards.

6. Pneumatic compression device (1) according to claim 5, further comprising a second fastening system (17) adapted to tighten the attachment member (2) to the body.

7. A pneumatic compression device (1) according to any one of claims 2 to 6, wherein the at least one primary airbag (5) is attached to the second layer (4) along its inner edge (5 a) and to the first layer (3) along its peripheral surface (5 b) and to the attachment means (2) along its lower edge surface (5 c).

8. The pneumatic compression device (1) of any one of the preceding claims, further comprising at least one adjustable strap (10) to secure the device (1) under, around or above the chin of the subject.

9. The pneumatic compression device (100) of claim 1, wherein the at least one primary airbag (5) is configured with a plurality of sleeves (108) to accommodate fingers of the subject's hand or toes of the foot.

10. The pneumatic compression device (100) of claim 1 or claim 9, wherein the at least one primary airbag (5) is configured as a single sleeve that accommodates the entire hand or the foot of the subject.

11. The pneumatic compression device (100) of any of claims 1, 9 or 10, further comprising a first securing member (102) to secure the device (100) in place.

12. A pneumatic compression device (100) according to any of claims 1, 9, 10 or 11, further comprising a second securing means (103) to secure the device (100) in place.

13. The pneumatic compression device (1, 100) according to any one of the preceding claims, wherein the attachment member (2), the first fastening system (16), the second fastening system (17), the first securing member (102) or the second securing member (103) is capable of tightening the device (1, 100) against the surface of the scalp, foot or hand with a larger force by means of a pull cord mechanism.

14. A pneumatic compression device (200) for preventing or treating chemotherapy-induced infertility in a subject receiving chemotherapy treatment, the device (200) comprising: at least one primary airbag (205), an applicator (202) adapted to receive the at least one primary airbag (205), and a cap (204) configured to receive the at least one primary airbag (205) within the applicator (202) when deflated, wherein the at least one primary airbag (205) located within the applicator (202) is configured to be inflated with air or gas at ambient temperature and to exert a compressive pressure when the airbag (205) is inflated.

15. The pneumatic compression device (200) of claim 14, further comprising an outer shell (210) and an inner shell (212) that combine to form a housing (214) that houses the at least one primary airbag (205).

16. The pneumatic compression device (200) of claim 14 or claim 15, further comprising a support member (208) housed inside the applicator (202) and in communication with the cap (204).

17. The pneumatic compression device (200) of claim 16, wherein the support member (208) is surrounded by the at least one primary airbag (205).

18. The pneumatic compression device (200) of any of claims 14-17, wherein the cap (204) is reversibly connected to the applicator (202) and is released from the applicator (202) when the at least one primary airbag (205) is inflated.

19. The pneumatic compression device (200) of any of claims 14-17, wherein the cap (204) is fixed to the applicator (202) and further comprises an aperture (206) through which the at least one primary airbag (205) is pushed prior to inflation.

20. Pneumatic compression device (1, 100, 200) according to the preceding claim, further comprising a control element (9).

21. The pneumatic compression device (1, 100, 200) according to claim 20, wherein the control element (9) comprises a pump, a pressure sensor and a tissue perfusion sensor.

22. The pneumatic compression device (1, 100, 200) of claim 21, wherein the pressure sensor is in communication with the at least one primary airbag (5, 205).

23. The pneumatic compression (1, 100, 200) device of any one of the preceding claims, wherein the at least one primary airbag (5, 205) further comprises a plurality of airbag compartments, each airbag compartment operating independently of the other.

24. The pneumatic compression device (1, 100, 200) of any one of claims 1-22, wherein the at least one primary airbag (5, 205) further comprises a plurality of airbag compartments, each of the plurality of airbag compartments being in fluid communication with an airbag compartment juxtaposed thereto.

25. A pneumatic compression device (1, 100, 200) according to claim 23 or claim 24, wherein the at least one main bladder (5, 205) or the plurality of bladder compartments is connected to the pump having a two-way valve system to control the inflow and outflow of the fluid.

26. The pneumatic compression device (1, 100, 200) of any one of the preceding claims, wherein the device (1, 100, 200) applies a compression pressure between about 20mmHg and about 100mmHg to the subject when activated.

27. The pneumatic compression device (1, 100, 200) of claim 26, wherein the compression pressure applied is between about 25mmHg and about 75 mmHg.

28. A pneumatic compression device (1, 100, 200) according to claim 26 or claim 27, wherein the compression pressure applied is between about 40mmHg and about 60 mmHg.

29. A pneumatic compression device (1, 100, 200) according to any of the preceding claims, wherein the compression pressure is applied incrementally.

30. Pneumatic compression device (1, 100, 200) according to claim 29, wherein the compression pressure is applied uniformly and/or non-uniformly.

31. The pneumatic compression device (1, 100, 200) of any one of the preceding claims, further comprising a foam layer inserted within the at least one primary airbag (5, 205) or one or more of the plurality of airbags; wherein the foam layer applies a reactive force through the bladder to the scalp, foot, hand or cavity as air is incrementally evacuated to create a vacuum within the at least one primary bladder (5, 205) or one or more of the plurality of bladders.

32. A pneumatic compression device (1, 100) according to any of the preceding claims, wherein a fluid or solid in the form of a solid at ambient pressure and a fluid or solid in the form of a solid at a pressure below atmospheric pressure is inserted into one or more of the at least one main balloon (5) or the plurality of balloons, wherein the fluid or the sales harden when the pressure within the at least one main balloon (5) decreases, thereby generating a modifiable compression force against the tissue.

33. A pneumatic compression device (1, 100, 200) according to any of the preceding claims, wherein the at least one primary airbag (5, 205) or the plurality of airbags is inflated to a predetermined pressure level below a target therapeutic pressure level before a user uses the device (1, 100, 200).

34. The pneumatic compression device (1, 100, 200) of any one of the preceding claims, wherein the at least one primary airbag (5, 205) or the plurality of airbags are provided at a predetermined pressure level and are not further inflated.

35. A pneumatic compression device (1, 100, 200) according to any of the preceding claims, wherein the attachment means (2) further comprises at least one status indicator light (13).

36. A method of controlling delivery of a drug to a target site on a body via a blood vessel, the method comprising:

maintaining the compressive force for a predetermined period of time; and

releasing the compressive force applied to the tissue at the target site at a predetermined rate and in a predetermined geometric pattern.

37. The method of claim 36, wherein the compressive force is applied to the tissue site upstream of an intended site of action.

38. The method of claim 36 or claim 37, wherein the compressive force of about 20mmHg to about 100mmHg is applied to the skin/surface tissue at the target site.

39. The method of any one of claims 36-38, wherein the compressive force applied is configured to mechanically occlude microvasculature proximate the surface of the tissue and a local arterial supply vessel.

40. The method of any one of claims 36-39, wherein the compressive pressure is applied uniformly across the tissue site to be treated.

41. The method of any one of claims 36-40, wherein the compressive force is maintained for a period of time between 30 minutes and 7 hours.

42. The method of any one of claims 36-41, wherein the compressive force is applied at different regions of the tissue.

43. The method of any one of claims 36-42, wherein the compressive force is applied in a pulsating manner.

44. A method of controlling drug delivery to a target site on a body, followed by reactivating blood flow for a period of time to ensure long-term tissue viability, the method comprising:

mechanically compressing the skin/surface tissue at the target site with a predetermined compression force to cause occlusion of local microvasculature;

maintaining microvascular occlusion for a predetermined period of time such that drugs circulating through the vascular system do not reach the target site or a site downstream of the target site;

Releasing the occlusion at a predetermined rate and in a predetermined geometric pattern in a controlled manner;

sensing a physiological parameter;

adjusting the mechanical compression applied to the tissue site based on the sensed physiological parameter; and

Applying a compressive force to the skin tissue in a pulsatile manner to promote blood flow, thereby allowing the removal of the waste agent from the local vascular structure.

45. The method of claim 44, wherein the sensed physiological parameter is the blood perfusion in the tissue site being treated.